Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Blood pressure lowering provides protection against intracranial bleeding in patients with cerebrovascular disease, including those on antithrombotic therapy, according to results of a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke trial.

In an email to Reuters Health, Dr. John Chalmers of The George Institute for Global Health, University of Sydney, Australia, explained the purpose of the substudy. “We wished to see if the benefits of BP lowering after stroke, as reported in main results of PROGRESS, were also evident in the subgroup receiving antithrombotic therapy. We wished to investigate whether BP lowering might offer a useful strategy to combat the well established risks of bleeding in patients receiving antithrombotic therapy.”

“The main take home message for clinicians,” he said, “is that yes, BP lowering does protect against the most feared complication of antithrombotic therapy – intracranial bleeding – and should be considered not just when this therapy is prescribed for patients with cerebrovascular disease, but in all patients given antithrombotics who have elevated blood pressure, or other risk factors for intracranial bleeding.”

Results of the PROGRESS trial were published in 2001 in The Lancet and reported by Reuters Health at that time. (See Reuters Health story of Sept 27, 2001). Briefly, the trial randomly assigned 6105 patients to active treatment with the angiotensin-converting enzyme inhibitor perindopril (with or without the diuretic indapamide at the physician’s discretion) or matching placebo(s).

All patients in the trial had a history of stroke or transient ischemic attack, and 48% were classified as hypertensive at the first visit. At baseline, 4876 (80%) patients were on antithrombotic therapy.

During a mean follow-up of 3.9 years, 119 intracranial and 123 extracranial bleeding events occurred. Among patients with and without antithrombotic therapy, active treatment lowered BP by 8.9/4.0 and 9.3/3.8 mm Hg and reduced the risks of intracranial bleeding by 46% and 70%, respectively, the researchers report.

Among patients on antithrombotic therapy, those with the lowest follow-up systolic blood pressure (median, 113 mm Hg) had the lowest risk of intracranial bleeding.

Active treatment did not reduce the risks of extracranial bleeding significantly in either group.

Dr. Chalmers and colleagues note in their paper that, “Separate observational analyses have also shown that the lowest achieved follow-up systolic BP down to approximately 115 mm Hg was associated with the lowest incidence of intracranial bleeding in patients on antithrombotic therapy. These findings are supported by a number of prospective cohort studies, which demonstrated significant associations between BP and antithrombotic therapy-related bleeding.”

The present findings are also consistent with ACTIVE-I trial, which demonstrated 40% reduction in intracranial bleeding associated with BP lowering in patients with atrial fibrillation on antithrombotic therapy. (See Reuters Health story of Mar. 9, 2011).